Stereoselective Synthesis of Nipecotic Acid Derivatives via Palladium-Catalyzed Decarboxylative Cyclization of γ-Methylidene-δ-valerolactones with Imines

A new synthetic method of multisubstituted nipecotic acid (piperidine-3-carboxylic acid) derivatives has been developed by way of palladium-catalyzed decarboxylative cyclization of γ-methylidene-δ-valerolactones with imines. By employing the diethoxyphosphinoyl group as the N-protecting group for imines, the reaction proceeds smoothly with high diastereoselectivity. The products thus obtained can be further derivatized with high efficiency under simple reaction conditions.